Disturbance of pro-oxidative/antioxidative balance in allogeneic peripheral blood stem cell transplantation

High dose chemotherapy causes increased free radical formation and depletion of tissue antioxidants. Whether allogeneic hematopoietic stem cell transplantation (HSCT) has an effect on oxidative stress is uncertain. The aims of the study were to determine the effect of allogeneic HSCT on plasma concentrations of antioxidants and oxidative stress biomarkers, and to investigate their relationships with graft-versus-host disease (GVHD), conditioning regimens, and transplant-related mortality (TRM) in patients with hematological malignancies. Patients (n=25) undergoing allogeneic HSCT from HLA-matched sibling donors were enrolled in the study. Plasma oxidant and antioxidant status were measured at day -1 before transplantation and 30 days after HSCT. In both myeloablative (n=14) and non-myeloablative (n=11) transplant groups, the mean levels of plasma malondialdehyde (MDA) and nitric oxide (NO) increased after allogeneic HSCT (p <0.01), whereas superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities decreased compared with baseline values (p <0.01). No significant relationships were found between either the pretransplant or post-transplant mean levels of the oxidative stress parameters and the existence of graft-versus-host disease (GVHD), the type of conditioning regimen, or transplant related mortality (TRM). This study documents a significant disturbance of pro-oxidative/antioxidative balance in the plasma of patients undergoing allogeneic HSCT regardless of the intensity of the conditioning regimen.     

Lack of association of 5 SNPs in the vicinity of the insulin-degrading enzyme (IDE) gene with late-onset Alzheimer's disease

Insulin-degrading enzyme (IDE) is a strong biological and positional candidate gene for Alzheimer's disease (AD). Previously some studies have examined the role of common variation in the IDE gene with AD risk but the results have been inconsistent. In this study we examined the role of 5 SNPs that define a linkage disequilibrium (LD) block spanning 276kb around IDE. Our sample comprised up to 1012 late-onset AD (LOAD) cases and 771 older white controls. In addition, we also examined the association of these SNPs with quantitative measures of AD progression, namely age-at-onset (AAO), disease duration and Mini-Mental State Examination (MMSE) score. None of the SNPs examined in this fairly large case-control sample revealed significant association with AD risk. These SNPs also showed no significant association with AD quantitative traits.     

Antimeasles antibodies in preterm infants during early infancy in Turkey

AIM: To measure maternally derived measles antibodies in sera of premature infants at birth and seropositivity rates in early infancy in a rural area of central Turkey. METHODS: 65 premature and 24 full-term infants born in Erciyes University Hospital and their mothers were recruited to a longitudinal, prospective study. The infants were divided into three groups by gestational age: group A, <33 weeks; group B, 33-37 weeks; group C, >37 weeks. For specific analyses, the groups were subdivided into groups Al, B1 and C1 (infants of naturally immunised mothers) and A2, B2 and C2 (infants of vaccinated mothers). Blood samples were obtained from mothers and infants after delivery. The infants were re-evaluated at 2, 4 and 6 months of age. RESULTS: Of 25 mothers, 20.3% were seronegative for measles antibodies. Twenty of the mothers had not been vaccinated. The percentages of seronegative infants at birth were 24.2% (n=8), 12.5% (n=4) and 0% (n=0) in groups A, B and C, respectively. No infants were seronegative at birth in Al, B1 or C1. Mean levels of antimeasles antibodies in all naturally immunised mothers were significantly higher than in vaccinated mothers. Antibody levels in all infants decreased rapidly with increasing age. Gestational age at birth [beta=0.179, t=3.359, 95% confidence interval (CI) 0.0001-0.0001, p<0.05], birthweight (beta=0.637, t=9.691, 95% CI 0.057-0.086, p<0.05) and maternal naturally immunised status (beta=0.168, t=2.825, 95% CI 0.002-0.014, p<0.05) were significantly associated with antibody levels after birth. In all groups of naturally immunised mothers, the percentages of seronegative infants were significantly lower than in vaccinated mothers at birth and at 2, 4 and 6 months of age. CONCLUSION: The current recommendation to immunise all infants at 9 months of age might require revision for premature infants, especially those whose mothers have vaccination-induced immunity.     

Effect of parenterally l-arginine supplementation on the respiratory distress syndrome in preterm newborns

l-Arginine (l-Arg) is the precursor of nitric oxide which plays an important role on pulmonary circulation and pulmonary vascular tone. Earlier studies suggested that l-Arg levels in preterm newborns with respiratory distress syndrome (RDS) were low due to its consumption and l-Arg supplementation may reduce the severity of RDS. Our aim was detect the effect of the parenterally l-Arg supplementation on RDS severity. The subjects were chosen between preterm newborns (gestational age <34 weeks) (n?=?30). Twenty of the subjects were diagnosed with permaturity and RDS, and 10 of the subjects were healthy preterm newborns. Ten of the subjects was taken l-Arg (1.5?mmol/kg/d) in addition to routine RDS treatment and assumed as “Group 1”. In this group, daily l-Arg supplementation was started end of the first day, and continued at end of fifth day. The others of the subjects diagnosed with RDS was take routine RDS treatment and assumed as “Group 2”. Healthy preterm newbors assumed as “Group 3”. Blood collections for l-Arg levels via tandem mass spectrometry were made in first day and repeated on the seventh days. Oxygenation index was used to determine severity of RDS. l-Arg consentrations in Group 1 were 8.7?±?4.1?μM/L and 11.9?±?5.0?μM/L in first and seventh day, respectively. l-Arg consentrations were 12.6±4.5?μM/Land 10.9?±?5.4?μM/L in Group 2 and 8.6?±?5.1?μM/L and 9.4?±?4.1?μM/L in Group 3. There is no correlation between l-Arg concentrations and OI also duration of the mechanical ventilation of the subjects in patient groups (Group 1 and 2).     

Placental levels of total oxidative and anti-oxidative status,ADAMTS-12 and decorin in early- and late-onset severe preeclampsia

Objective: Preeclampsia (PE), can be classified according to the timing of disease onset: early-onset PE occurs before the 34th gestational week and late-onset PE occurs in the 34th gestational week or later. The aim of this study was to determine whether total antioxidant status (TAS), and total oxidant status (TOS), ADAMTS-12 and decorin levels differ among early-onset severe PE (EOS-PE), late-onset severe PE (LOS-PE) and uncomplicated pregnancies.

Methods: In this case–control study, placental samples obtained from 25 pregnant patients with EOS-PE, 26 pregnant patients with LOS-PE and 28 healthy patients with uncomplicated pregnancies (control group).

Results: Placenta levels of decorin and TOS were significantly higher and TAS was significantly lower in the EOS-PE and LOS-PE groups than in the control group. These alterations were more prominent in patients with EOS-PE than in patients with LOS-PE. There were no significant differences in the ADAMTS-12 levels of the groups.

Conclusion: The distinctly higher rate of negative perinatal outcomes in both EOS-PE and LOS-PE patients is well evidenced. However, the main questions that need to be answered are whether the only difference between these two diseases is the time of their onset and whether the only difference between them with respect to fetal morbidity and mortality is prematurity.     

The effect of melatonin on liver superoxide dismutase activity, serum nitrate and thyroid hormone levels

Melatonin is a main neurohormone of the pineal gland. The effects of melatonin on the level of serum thyroid-stimulating hormone (TSH), thyroxine (T(4)), triiodothyronine (T(3)), nitrate, melatonin and liver superoxide dismutase (SOD) activity were examined in rats. Melatonin was injected at the dose of 10 mg/kg for 7 days, 2 h before turning the lights off. Rats were decapitated at 10:00 a.m. and 02:00 a.m., which are the times of the lowest and highest serum melatonin levels, respectively. Blood and tissue samples were collected. Decreased TSH, T(3), T(4) and nitrate levels were determined in the melatonin-injected and nighttime groups. Melatonin levels showed a diurnal rhythm. SOD activity increased in the melatonin-treated group. The results demonstrate that increased SOD activity, and reduced serum TSH, T(3), T(4) and nitrate levels correlated with the serum melatonin levels.     

A different approach to telomere analysis with ddPRINS in chronic lymphocytic leukemia

Telomeric sequences, located at the very end of the chromosomes, compensate for the chromosomal shortening as it happens after each round of cell division. Telomeric sequences influence the progress of cellular senescence and cancer progression. It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia (CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique. Twenty patients with CLL and four healthy donors as a control group were included. We found short telomeres and no detectable telomeric repeats at the sites of chromosome fusion. We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span. These cells may have encountered many antigenic stimulants in the past and hence underwent multiple clonal expansions. Our findings imply that shortened telomeres in CLL may be reflecting the "history" of the disease and serve as an independent prognostic factor.     

A case of a sporadic malignant peripheral nerve sheath tumor of the urinary bladder with concomitant in situ urothelial carcinoma treated by transuretheral resection

Malignant peripheral nerve sheath tumor (MPNST) of the urinary bladder is a very rare clinical entity. The association of such a tumor with urothelial carcinoma is even more unusual. Differential diagnosis between coexisting two distinct primary tumors and carcinosarcoma of the urinary bladder is very important as both the treatment and prognosis vary widely. Herein, we report a case of an MPNST with a concomitant in situ urothelial carcinoma in a 53-year-old man. To our knowledge, this is the first documented case of MPNST of the bladder that is treated by transuretheral resection which is in contrast with the previous reports that used cystectomy.     

Does metformin affect mammographic breast density in postmenopausal women with type 2 diabetes

Abstract

Background: Increased mammographic breast density (MBD) is known to be associated with an increased risk of developing breast cancer.

Aims: In this study, we aimed to research the possible relationship between MBD and metformin use in postmenopausal women diagnosed with type 2 diabetes mellitus (T2DM).

Method: The patients were divided into two groups: women with T2DM and who were on metformin and women who were newly diagnosed with T2DM and had not yet taken metformin. MBD types are evaluated by a specialist radiologist.

Results: Among the 74 women, 32 (43.2%) were in the group that did not use metformin and 42 (56.8%) were in the group of patients using metformin. The duration of breastfeeding (p?=?.0003), fasting blood glucose (p?=?.0003) and HbA1c (p?=?.0006) were statistically significantly higher in the group not using metformin. The quantitative mean ranks of the group members’ MBD’s were 41.81 in the metformin naïve group and 34.21 in the group using metformin (p?=?.12).

Conclusions: In conclusion, metformin has no statistically significant effect on MBD in postmenopausal female patients with T2DM.